Vitamin C treatment promotes mesenchymal stem cell sheet formation and tissue regeneration by elevating telomerase activity

Abstract

Cell sheet engineering has been developed as an alternative approach to improve mesenchymal stem cell-mediated tissue regeneration. In this study, we found that vitamin C (Vc) was capable of inducing telomerase activity in periodontal ligament stem cells (PDLSCs), leading to the up-regulated expression of extracellular matrix type I collagen, fibronectin, and integrin β1, stem cell markers Oct4, Sox2, and Nanog as well as osteogenic markers RUNX2, ALP, OCN. Under Vc treatment, PDLSCs can form cell sheet structures because of increased cell matrix production. Interestingly, PDLSC sheets demonstrated a significant improvement in tissue regeneration compared with untreated control dissociated PDLSCs and offered an effective treatment for periodontal defects in a swine model. In addition, bone marrow mesenchymal stem cell sheets and umbilical cord mesenchymal stem cell sheets were also well constructed using this method. The development of Vc-mediated mesenchymal stem cell sheets may provide an easy and practical approach for cell-based tissue regeneration.

Application of the cell sheet technique in tissue engineering

“…Cardiomyocytes cultured on these dishes formed a myocardial cell sheet within 4 days. (12) cultured periodontal ligament stem cells treated with vitamin C (Vc) at various concentrations. The cells form cell sheet structures at concentrations of Vc >20 µg/ml, as Vc can increase cell matrix production.…”

Improving the osteogenesis of human bone marrow mesenchymal stem cell sheets by microRNA-21-loaded chitosan/hyaluronic acid nanoparticles via reverse transfection

“…5 Cell sheets were recently induced using a vitamin C (Vc) inducing method because of increased cell matrix production and deposition. 6 This cell processing approach could effectively preserve …”

Efficiently engineered cell sheet using a complex of polyethylenimine–alginate nanocomposites plus bone morphogenetic protein 2 gene to promote new bone formation

“…The cells were cultured in medium containing Vc (20 µg/mL, Sigma-Aldrich) for 10 days until cell sheet formation, and the cell sheet was lifted using a scraper ( Figure 1B). 12 There were two kinds of cell sheets: BMP-2 gene-modified BMSC cell sheet (BMP/CS) and EGFP gene-modified BMSC cell sheet (EGFP/CS).…”

“…10,11,32 In this study, Vc was added to create cell sheet, because of its properties of increasing cell proliferation and ECM biosynthesis. 12 Liu et al 33 also found that BMSC sheet could evidently enhance osteogenic differentiation compared with BMSCs, which because of the cell sheet enriches ECM and plays an important role in regulating the cell differentiation.…”

“…[8][9][10] The cell sheet made by these methods not only maintains the connections between cells and ECM but also makes it easy to transplant for bone defect treatment. 10, 11 Wei et al 12 developed a method by which vitamin C (Vc) alone was used to induce the cell sheet formation, which provided an easy and practical tissue engineering approach. In this study, we obtained a Vc-based bone marrow mesenchymal stem cell (BMSC) sheet, which was modified by bone morphogenetic protein-2 (BMP-2) gene.…”